Scientists close to safer testing of unborn babies

The ability to test a pregnant woman's blood to assess the health of her unborn child with high reliability, without risk and much earlier, moves a step closer today.

Scientists have found a way to locate the traces of foetal DNA in a mother's blood, allowing the ability to diagnose serious genetic disorders without invasive procedures such as amniocentesis.

Researchers have known for more than three decades that a few foetal cells are present in a pregnant woman's blood. Then in 1997 it was found that foetal DNA also circulates.

Prof Dennis Lo, of the Chinese University of Hong Kong, and colleagues report today in the Proceedings of the National Academy of Sciences that they have found a new label for foetal DNA which exists outside cells, so it can be distinguished and analysed.

Although low concentrations of foetal DNA have been detected in the blood plasma of pregnant women, the lack of a molecular marker to differentiate it from the high levels of maternal DNA has limited its clinical usefulness.

To find a universal marker of foetal DNA, Prof Lo and his team searched for "epigenetic" differences, chemical changes to DNA that do not alter the genetic code itself but the way the body uses it.

In a gene called maspin, Prof Lo found that a particular type of chemical modification, methylation, occurs at much higher levels in maternal DNA than foetal DNA. Unmethylated foetal DNA was detected in maternal blood plasma in all three trimesters.

The unmethylated DNA disappeared within 24 hours of birth, indicating that it is specific to pregnancy.

The results show that it is possible to find universal epigenetic markers for foetal DNA in maternal blood and may provide the basis for developing novel, non-invasive methods for prenatal diagnosis and foetal monitoring. "We believe that this study represents a significant step forward," said Prof Lo.

His group has shown how circulating foetal DNA could be used to diagnose potentially lethal conflicts in Rh factor, a protein on red blood cells. If an Rh-negative woman carries an Rh-positive foetus, her immune system can create antibodies against the baby's blood cells, causing anaemia.

Teams are also studying how to detect mutations passed on from the father.

Conventional tests rely on obtaining foetal cells directly. Amniocentesis is performed at 15 to 18 weeks' gestation, when a needle is used to collect amniotic sac fluid.

Chorionic villus sampling can be done as early as 10 weeks, when a sample is taken from the mat of chorionic villi, or finger-like projections on the foetal side of the early placenta.

Both carry up to a one per cent risk of miscarriage, so they are only usually used when blood tests suggest that there may be a problem. If shown positive for serious disease, mothers are given the option of an abortion.

Using epigenetic markers offered a new way to detect the genetic material from the baby that circulated in the bloodstream of pregnant women, offering the prospect of a safer and earlier way to screen the foetus for genetic disorders, said Prof Lo.

He said that although specialised and relatively laborious methods were required, new technology should simplify the procedure.

But easier foetal DNA testing may raise ethical questions. Some researchers worry that gender tests will lead to abortions when parents want a baby of a given sex.

If foetal DNA testing can one day routinely show whether an early foetus has genes that predispose it to cancer or other diseases, parents-to-be could face very difficult decisions.